Shares of Mirati Therapeutics MRTX were down 23% after it announced preliminary data from first-line lung cancer studies on its KRAS inhibitor drug adagrasib plus Merck’s MRK PD-1/L1 checkpoint inhibitor Keytruda.
The KRYSTAL-7 phase II study evaluated adagrasib plus Keytruda for the treatment of previously untreated non-small cell lung cancer (NSCLC) in patients harboring a KRASG12C mutation across all PD-L1 subgroups.
Data from the study showed that adagrasib plus Keytruda led to promising preliminary clinical activity across all PD-L1 subgroups with an objective response rate (ORR) of 49% among patients who were clinically evaluable and received at least one on-study scan. The combination of this KRASG12C inhibitor and a PD-1/L1 checkpoint inhibitor showed a good safety profile.
In the first-line NSCLC cohort of another study, KRYSTAL-1 phase Ib, the ORR was 57% and the disease control rate was 100% among the seven evaluable patients enrolled in the study.
Mirati said that the data from cohorts of both studies showed that the combination of this KRASG12C inhibitor and a PD-1/L1 checkpoint inhibitor could offer a chemotherapy-free option for treating first-line NSCLC patients. Based on this data, Mirati plans to initiate phase III studies.
However, investors seem unimpressed with the data readout and are questioning if adagrasib is commercially viable for first-line treatment of NSCLC. The ORR of 49% seen in the KRYSTAL-7 study is generally in line with chemotherapy + Keytruda, which showed around 48% ORR across all PD-L1 subgroups in the KEYNOTE-189 study. Keytruda + chemotherapy is the current standard of care in first-line NSCLC. However, a matured dataset is needed, including overall survival and progression-free survival data, to make any meaningful comparison to the standard of care.
This year so far, the stock price of Mirati has plunged 51.2% compared with the industry’s decline of 17.8%.
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Mirati has long been a takeover target and last month the stock was up on rumors that big cancer drugmakers may offer to buy the company. Mirati’s new drug application (NDA), seeking approval for adagrasib for previously-treated KRASG12C-mutated NSCLC is under review with the FDA. A decision by the FDA is expected by Dec 14, 2022. A marketing authorization application is also under review in Europe.
Potential buyers could be Pfizer, Bristol-Myers BMY, Merck or AstraZeneca, per an article on Investor's Business Daily. Mirati did not issue any press release or make any comment on the buyout speculations. There are currently no formal offers and a deal is not imminent.
Mirati is evaluating adagrasib — both as monotherapy and combinations — in multiple cohorts of phase I/II KRYSTAL-1 study across multiple solid tumors that harbor KRAS G12C mutations. Other than the combination of adagrasib with Merck’s Keytruda in NSCLC, as discussed above, adagrasib is being evaluated in combination with Boehringer Ingelheim’s Gilotrif (afatinib) in advanced NSCLC and Bristol-Myers’ Erbitux (cetuximab) in advanced colorectal cancer or CRC.
Adagrasib, if approved, will face competition from Amgen’s AMGN KRAS G12C inhibitor, Lumakras, which was approved for second-line NSCLC in the United States in 2021 and Europe in January 2022. It is now launched in more than 45 countries. Amgen’s Lumakras is off to an excellent start, while its label expansion studies, which have the potential to significantly expand the currently addressable patient population, are progressing rapidly.
Earlier this year, Amgen announced data from a phase Ib study, which included mostly pre-treated NSCLC population, combining Lumakras with immunotherapy [Tecentriq (atezolizumab) or Merck’s Keytruda (pembrolizumab)]. The study showed an ORR of 29% in this patient group. However, in the study, Amgen reported that Lumakras with immunotherapy led to higher enzyme elevations.
Mirati currently has a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.
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